鉴定 COX4I2 为一个低氧相关基因，通过 FGF1 促进 CRC 中的 EMT 和血管生成。

Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC.

机构信息

Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, 215600, Jiangsu, China.

Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, Jiangsu, China.

出版信息

Cell Mol Biol Lett. 2022 Sep 5;27(1):76. doi: 10.1186/s11658-022-00380-2.

BACKGROUND

Current evidence suggests that the hypoxic tumor microenvironment further aggravates tumor progression, leading to poor therapeutic outcomes. There is as yet no biomarker capable of evaluating the hypoxic state of the tumor. The cytochrome c oxidase (COX) subunit is crucial to the mitochondrial respiratory chain.

METHODS

We investigated the potential oncogenic role of COX subunit 4 isoform 2 gene (COX4I2) in colorectal cancer (CRC) by least absolute shrinkage and selection operator (LASSO) and COX regression analysis to examine whether COX4I2 overexpression can predict colorectal cancer (CRC) prognosis. The association of COX4I2 levels with clinical features and its biological actions were evaluated both in vitro and in vivo.

RESULTS

Our analysis showed that elevated COX4I2 levels were correlated with poor clinical outcomes. We also observed that that COX4I2 may be involved in epithelial-mesenchymal transition, activation of cancer-related fibroblasts and angiogenesis in relation to fibroblast growth factor 1.

CONCLUSIONS

The COX4I2 level may be a predictor of outcome in CRC and may represent a novel target for treatment development.

背景

目前的证据表明，缺氧的肿瘤微环境进一步加重了肿瘤的进展，导致治疗效果不佳。目前还没有能够评估肿瘤缺氧状态的生物标志物。细胞色素 c 氧化酶（COX）亚基是线粒体呼吸链的关键。

方法

我们通过最小绝对收缩和选择算子（LASSO）和 COX 回归分析，研究细胞色素 c 氧化酶亚基 4 同工型 2 基因（COX4I2）在结直肠癌（CRC）中的潜在致癌作用，以检验 COX4I2 过表达是否可以预测结直肠癌（CRC）的预后。评估了 COX4I2 水平与临床特征的相关性及其在体外和体内的生物学作用。